Mammalian Mitochondrial ADP/ATP Transporters

Since we first identified the 4th member of mammalian adenine nucleotide translocase (ANT) genes about a decade ago, we have been studying function and regulation of mammalian Ant paralogs. ANTs are the most abundant proteins in mitochondria and primarily exchange the ADP/ATP through the mitochondrial inner membrane (MIM), thus they play an essential role in bioenergetics in eukaryotes. ANTs have also been implicated in regulation of the mitochondrial permeability transition pore (MPTP) and are implicated in uncoupling, and therefore may also play a role in the control of cellular survival and death. All eukaryotes have multiple ANT family genes (paralogs), and their gene expression is differentially regulated. In some cases, expression is presumably dependent on the extracellular oxygen and nutrient environment, and in other cases, expression is controlled in a tissue-specific manner. Using mouse genetics, yeast genetics and biochemical approaches, we are identifying both specific and redundant roles of ANT paralogs in mammalian development, homeostasis and disease.